Apparatus and method for ranging and noise reduction of low coherence interferometry lci and optical coherence tomography oct signals by parallel detection of spectral bands

ABSTRACT

Apparatus and method for increasing the sensitivity in the detection of optical coherence tomography and low coherence interferometry (“LCI”) signals by detecting a parallel set of spectral bands, each band being a unique combination of optical frequencies. The LCI broad bandwidth source is split into N spectral bands. The N spectral bands are individually detected and processed to provide an increase in the signal-to-noise ratio by a factor of N. Each spectral band is detected by a separate photo detector and amplified. For each spectral band the signal is band pass filtered around the signal band by analog electronics and digitized, or, alternatively, the signal may be digitized and band pass filtered in software. As a consequence, the shot noise contribution to the signal is reduced by a factor equal to the number of spectral bands. The signal remains the same. The reduction of the shot noise increases the dynamic range and sensitivity of the system.

CROSS REFERENCE TO RELATED APPLICATION

The present application is a divisional of U.S. patent application Ser.No. 10/501,276, filed Jul. 9, 2004, which is U.S. National Phase ofInternational Application No. PCT/US03/02349 filed Jan. 24, 2003. Thisapplication also claims benefit of copending U.S. provisional patentapplication No. 60/351,904, filed Jan. 24, 2002, entitled APPARATUS ANDMETHOD FOR RANGING AND SHOT NOISE REDUCTION OF LOW COHERENCEINTERFEROMETRY (LCI) AND OPTICAL COHERENCE TOMOGRAPHY (OCT) SIGNALS BYPARALLEL DETECTION OF SPECTRAL BANDS, and copending U.S. applicationSer. No. 10/136,813, filed Apr. 30, 2002, entitled METHOD AND APPARATUSFOR IMPROVING IMAGE CLARITY AND SENSITIVITY IN OPTICAL COHERENCETOMOGRAPHY USING DYNAMIC FEEDBACK TO CONTROL FOCAL PROPERTIES ANDCOHERENCE GATING, both commonly assigned to the assignee of the presentapplication. The disclosures of all these applications are incorporatedherein by reference in their entireties.

FIELD OF THE INVENTION

The present invention relates to apparatus, method, logic arrangementand storage medium for dramatically increasing the sensitivity in thedetection of optical coherence tomography and low coherenceinterferometry signals by detecting a parallel set of spectral bands,each band being a unique combination of optical frequencies.

BACKGROUND OF THE ART

Two methods currently exist to implement depth ranging in turbid media.The first method is known as Low Coherence Interferometry (“LCI”). Thismethod uses a scanning system to vary the reference arm length andacquire the interference signal at a detector and demodulating thefringe pattern to obtain the coherence envelope of the source crosscorrelation function. Optical coherence tomography (“OCT”) is a meansfor obtaining a two-dimensional image using LCI. OCT is described bySwanson et al. in U.S. Pat. No. 5,321,501. Multiple variations on OCThave been patented, but many suffer from less than optimal signal tonoise ratio (“SNR”), resulting in non-optimal resolution, low imagingframe rates, and poor depth of penetration. Power usage is a factor insuch imaging techniques. For example in ophthalmic uses, only a certainnumber of milliwatts of power is tolerable before thermal damage canoccur. Thus, boosting power is not feasible to increase SNR in suchenvironments. It would be desirable to have a method of raising the SNRwithout appreciably increasing power requirements.

A second method for depth ranging in turbid media is known in theliterature as spectral radar. In spectral radar the real part of thecross spectral density of sample and reference arm light is measuredwith a spectrometer. Depth profile information is encoded on thecross-spectral density modulation. Prior designs for spectral radar isprimarily found in the literature.

The use of spectral radar concepts to increase the signal to noise ratioof LCI and OCT have been described earlier. However, in thisdescription, only the real part of the complex spectral density ismeasured and the method uses a large number of detector elements (about2,000) to reach scan ranges on the order of a millimeter. It would bedesirable to have a method that would allow for an arbitrary number ofdetector elements. Secondly, the previously described method uses asingle charge coupled device (“CCD”) to acquire the data. Since thecharge storage capacity is limited, it requires a reduction of thereference arm power to approximately the same level as the sample armpower, giving rise to auto correlation noise on the sample arm light. Inaddition, since no carrier is generated, the 1/f noise will dominate thenoise in this system. Thirdly, even with the short integration times ofstate of the art CCD technology, phase instabilities in theinterferometer reduce fringe visibility of the cross spectral densitymodulation.

SUMMARY OF THE INVENTION

The present invention can increase the SNR of LCI and OCT by splittingthe LCI broad bandwidth source into a number “N” of spectral bands. Inone exemplary embodiment, the N spectral bands are individually detectedand processed to provide an increase in the SNR by a factor of N. Thisincrease in SNR enables LCI or OCT imaging by a factor of N timesfaster, or alternatively allows imaging at the same speed with a sourcethat has N times lower power. As a result, the present inventionovercomes two of the most important shortcomings of conventional LCI andOCT, namely, source availability and scan speed. The factor N may reachmore than 1,000, and allows construction of OCT and LCI systems that canbe more than three orders of magnitude improved from OCT and LCItechnology currently in practice.

The present invention improves current data acquisition speeds andavailability of sources for OCT. Shot noise is due to the statisticalfluctuations of the current that are due to the quantized or discreteelectric charges. The reduction of shot noise allows for much lowersource powers or much higher acquisition rates. Limitations in currentdata acquisition rates (approximately 4 frames/sec) are imposed byavailable source power and availability of fast mechanisms for scanningdelay. An increase in the sensitivity of the detection by a factor of 8would allow real time imaging at a speed of about 30 frames per second.An increase of the sensitivity by a factor of about 1,000-2,000 wouldallow for the use of sources with much lower powers and higher spectralbandwidths which are readily available, cheaper to produce, and cangenerate higher resolution LCI or OCT scans.

For ophthalmic applications of OCT, the efficient detection preferablyallows for a significant increase of acquisition speed. The limitationin ophthalmic applications is the power that is allowed to enter the eyeaccording to the ANSI standards (approximately 700 microwatts at 830nm). Current data acquisition speed in ophthalmic applications isapproximately 100-500 A-lines per second. The power efficient detectionwould allow for A-line acquisition rates on the order of about 100,000A-lines per second, or video rate imaging at about 3,000 A-lines perimage.

The gain in SNR is achieved because the shot noise has a white noisespectrum. An intensity present at the detector at frequency ω (orwavelength λ) contributes only to the signal at frequency ω, but theshot noise is generated at all frequencies. By narrowing the opticalband width per detector, the shot noise contribution at each frequencycan be reduced, while the signal component remains the same.

In summary, the present invention improves a performance of LCI and OCT,and as a result, can be used in developing LCI and OCT diagnostictechnologies for medical and non-medical applications.

Other features and advantages of the present invention will becomeapparent upon reading the following detailed description of embodimentsof the invention, when taken in conjunction with the appended claims.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention is illustrated in the drawings in which like referencecharacters designate the same or similar parts throughout the figures ofwhich:

FIG. 1 is a schematic view of a conventional system.

FIG. 2 is a schematic view of a preferred embodiment of the paralleldetection scheme for LCI.

FIG. 3 is a schematic view of a system with one detector array accordingto one embodiment of the present invention.

FIG. 4 is a detail of a probe.

FIG. 5 is a schematic view of separating unit in combination with twointegrating CCD arrays for detection of the dual-balanced wavelengthdemultiplexed signal.

FIG. 6 is a schematic view of a preferred embodiment of a standalonesystem

FIG. 7 is a schematic view showing spectral separating into 2 bands.

FIG. 8 is a schematic of spectral separating into 4 bands. The spectralresolution preferably used for each detector is twice as coarse as inthe case of multiplexing into 2 bands.

FIG. 9 is a schematic view of using beam recombination to provide onedimension of interference information along one dimension of atwo-dimensional detector array, while performing wavelength separatingalong the other dimension of the two dimensional array.

FIG. 10 is a schematic view of a phase tracking system according to oneembodiment of the present invention.

FIG. 1 is a flowchart depicting the reconstruction of LCI or OCT signalfrom wavelength bands.

FIG. 12 is a schematic view of a spectral domain OCT interferometerdesign with a source combining the spectra of several superluminescentsources.

FIG. 13 is a schematic view of a system with a four detector array.

FIG. 14 is a graph of a typical interference patter as a function ofpath length difference between sample arm and reference arm.

FIG. 15 is an embodiment of a phase tracker system with an extendedphase lock range.

FIGS. 15A-C are flow diagrams of a method.

FIG. 16 is a graph of frequency versus OCT power spectrum.

FIG. 17 is a graph of frequency versus amplitude spectrum subtractedfrom the shot noise (experimental data) for the N=1 (dotted line) andN=⅓ (solid line) cases.

FIG. 18 is a graph of power density for the full spectrum as a functionof frequency.

FIG. 19 is a graph after subtraction of the shot noise levels.

FIG. 20 is a graph after processing the signals.

FIG. 21 is a graph of the coherence envelope for the coherently summedchannels.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Overview

Certain exemplary embodiments of the present invention include a hybridmethod that implements aspects of LCI and OCT where the reference arm isscanned, and spectral radar, which does not require reference armscanning.

In one embodiment, the signal in the detection arm of an OCT system issplit into more than one spectral band before detection. Each spectralband is detected by a separate photodetector and amplified. For eachspectral band, the signal can be band pass filtered around the signalband by analog electronics and digitized, or, alternatively, the signalmay be digitized and band pass filtered in software. As a consequence,the shot noise contribution to the signal can be reduced by a factorequal to the number of spectral bands, while output of the signalremains the same. The reduction of the shot noise increases the dynamicrange and sensitivity of the system.

In another exemplary embodiment of the present invention, an apparatusis provided for spectral radar that does not require reference armscanning. For many detectors, no ranging or reference arm scanning isneeded, and the method may be similar to the method which can beemployed for a spectral radar except that phase information of the crossspectral density is preferably preserved.

In other exemplary embodiments, the present invention describes anarrangement for spectral radar that eliminate phase instability in theinterferometer, obtaining the complex spectral density and eliminatingauto correlation noise on the sample arm light, relative intensitynoise, and 1/f noise.

Theory

Time Domain Versus Spectral Domain OCT

Nearly all conventional OCT systems are based on Time Domain scanning.In such conventional systems, the length of the reference arm in aMichelson interferometer is rapidly scanned over a distancecorresponding to the imaging depth range. An alternative procedure toscanning the reference arm, is one that measures the cross-spectraldensity at the detection arm of the Michelson interferometer using aspectrometer. In Spectral Domain OCT, no mechanical (e.g., motionless)scanning of the reference arm is required, while an apparatus forgenerating a phase shift can be used. Only recently was it recognizedthat a significant signal to noise gain can be achieved by directmeasurement of the cross-spectral density.

FIG. 1 shows a schematic of a conventional Time Domain OCT system. Onscanning the reference arm path length, interference fringes are formedcorresponding to positions that match the distance to the threestructures drawn in the sample volume. A single detector is used todetect the interference fringes. By envelope detection of the fringepatterns, an image is constructed that maps tissue reflectivity to agiven location.

Certain exemplary embodiments of the present invention provide adetection principle based on Spectral Radar concepts (further referredto as Spectral Domain OCT) or a hybrid method between Spectral Domainand Time Domain OCT that can be more sensitive than current state of theart Time Domain OCT, allowing a substantial increase in the acquisitionspeed to resolution ratio.

Principle of Shot Noise Reduction in Spectral Domain OCT

The best signal to noise performance of Time Domain OCT systems isobtained when the noise is shot noise limited. Shot noise can be reducedsignificantly by replacing the single element detector with amulti-element array detector. When the detection arm light is spectrallydispersed on the array detector, each element of the array detects asmall wavelength fraction of the spectral width of the source. The shotnoise is preferably reduced by a factor equal to the number of elementsof the array. The principle of the signal to noise improvement is basedon the white noise characteristic of shot noise and the observation thatonly electromagnetic waves of the same wavelength produce interferencefringes.

The shot noise power density N_(shot)(f) (in units [W/Hz], [A²/Hz] or[V²/Hz]) is proportional to the current (or equivalently the opticalpower times the quantum efficiency) generated in the detector. For amonochromatic beam of wavelength λ₁ entering the interferometer, thefringe frequency or carrier f at the detector is determined by thevelocity v of the mirror, f₁=2v/λ₁. The shot noise is proportional tothe power (or spectral density S(ω)) at wavelength λ₁. A secondwavelength λ₂ is preferably coupled into the interferometer. A secondfringe frequency or carrier at frequency f₂=2v/λ₂ is simultaneouslypresent. The shot noise at this second frequency is preferably the sumof the shot noise generated by the optical power at wavelength λ₁ andλ₂. Also, at frequency f₁ the shot noise is the sum of the shot noisegenerated by the optical power at wavelength λ₁ and λ₂. Thus, at bothfrequencies a cross-shot noise term is generated by the simultaneouspresence of both wavelengths at the detector. By spectrally dispersingeach wavelength to a separate detector, the cross shot noise term can beeliminated. In this way, Spectral Domain OCT offers a significantimprovement of signal to noise ratio over Time Domain OCT systems.

Signal to Noise Analysis of Time Domain Versus Spectral Domain OCT.

Signal

Analysis of the Signal to Noise Ratio (SNR) in Time Domain OCT has beendescribed in related publications. The interference fringe peakamplitude in time domain OCT (is given by

I _(peak)=√{square root over (P _(ref) P _(sample))},  (1)

with P_(ref), P_(sample) the reference and sample arm power in Watts,respectively. In terms of electrical power at the detector, the signalin units [A²] is defined as

S=η ² e ₂ P _(ref) P _(samples) /E _(v) ²,  (2)

with η the quantum efficiency, e the charge quantum and E_(v)=hc/λ thephoton energy. The reference and sample arm powers are given by therespective reflected spectral densities,

P _(ref,sample) =∫S _(ref,sample)(ω)dω.  (3)

Assuming that the reference and sample spectral densities are equal tothe source spectral density S(ω), where the sample arm spectral densityis attenuated by a large factor, i.e., S_(ref)(ω)=S(ω),S_(sample)(ω)=αS(ω) with α<<1, and inserting the above expression ofreference and sample arm into the original definition of the signalgives,

S=η ² e ² α[∫S(ω)dω] ² /E _(v) ².  (4)

Thermal, Shot Noise and Relative Intensity Noise Contributions

Three contributions to the total noise of OCT signals are: thermalnoise, shot noise and relative intensity noise. Thermal noise isgenerated by the feedback resistor, shot noise is related to the finitenature of the charge quantum resulting in statistical fluctuations onthe current, and relative intensity noise is related to the temporalfluctuations due to chaotic character of classical light sources. Thesethree contributions to the noise density in units [A²/Hz] are given by,

$\begin{matrix}{{{N_{noise}(f)} = {\frac{4{kT}}{R_{fb}} + \frac{2\eta \; e^{2}P_{ref}}{E_{v}} + {2\left( \frac{\eta \; {eP}_{ref}}{E_{v}} \right)^{2}\tau_{coh}}}},} & (5)\end{matrix}$

k is Boltzmann's constant, T the temperature in Kelvin, R_(fb) the valueof the feedback resistor, and τ_(coh) the coherence time of the source.Coherence time is related to the full spectral width at half maximum Δλof a Gaussian source by the following relation, τ_(coh)=√{square rootover (2 ln 2/π)}λ₀ ²/(cΔλ). Shot noise limited detection is achievedwhen the second term in Eq. (5) dominates the other noise contributions.

Signal to Noise Ratio (SNR)

The signal to noise ratio (SNR) is given by

$\begin{matrix}{{{S\; N\; R} = \frac{S}{{N_{noise}(f)}B\; W}},} & (6)\end{matrix}$

with BW the signal bandwidth, and parameters S and N_(noise)(f) asdescribed above.

Space and Frequency Domain Description of the OCT Signal

The OCT signal is most easily described in the space domain. For asingle object in the sample arm, the interference term of the OCT signalis proportional to the real part of the Fourier transform of the sourcespectrum S(ω),

I(Δz)∝Re∫exp(ikΔz)S(k)dk,  (7)

with Δz the path length difference between sample and reference arm andk the wave vector. As a function of time, the OCT signal is given by,

I(t)∝Re∫exp(2iωtv/c)S(ω)dω,  (8)

with v the reference arm mirror velocity. The frequency spectrum of thesignal is given by a Fourier transform of the signal in the time domain,resulting in a complex function. The absolute value of this function isequal to the spectral density,

|I(f)|=|∫I(t)e ^(2iπft) dt|=S(πfc/v),  (9)

which shows that the signal bandwidth is directly proportional to thesource spectral width and scales linearly with the reference arm mirrorvelocity, i.e., imaging speed. Eq. (9) also directly relates theabsolute value of the frequency spectrum, |I(f)|, to the signal S (Eq.(4)).

Eq (9) also demonstrates that each angular frequency of the light sourceor equivalently each wavelength of the source is represented at its ownfrequency in the measured interferometric signal. The depth profileinformation I(t) can be obtained from the complex cross spectral densityI(f) by a Fourier transform.

The complex cross spectral density can also be obtained by splitting thesignal I(t) in several spectral bands using a dispersive orinterferometric element. At each detector, only part of the complexcross spectral density is determined. Combining the cross spectraldensities of each detector, the full spectral density of the signal isretrieved.

Thus, the same information can be obtained by separating spectralcomponents to individual detectors. Combining the signal of alldetectors in software or hardware would result in the same signal asobtained with a single detector.

Signal to Noise Gain with Spectral Domain OCT

In the detection arm, the spectrum can be split into two equal halves,where two detectors each detect one half of the spectrum. According toEq (9), the frequency spectra at detectors 1 and 2 are given by|I₁(f)|=S(πfc/v) for f<f₀, I₁(f)=0 for f>f₀ and I₂(f)=0 for f<f₀,|I₂(f)|=S(πfc/v) for f>f₀, respectively. The frequency spectrum as wouldbe acquired by a single detector in time domain OCT is given by the sumof I₁(f) and I₂(f); I(f)=I₁(f)+I₂(f). Thus, the signal S after combiningthe spectra is equal, however I₁(f)=0 for f>f₀ and I₂(f)=0 for f<f₀, thebandwidth BW per detector can be reduced by a factor of 2.

The noise is determined by the sum of the shot noise contributions atdetectors one and two. From Eqs. (5) and (6), the shot noise perdetector is proportional to the reference arm power at the detectortimes the bandwidth for the detector. Since the spectrum was split inequal halves, the reference power at detectors 1 and 2 is, respectively,

P_(ref) ¹=0.5P_(ref), P_(ref) ²=0.5P_(ref).  (10)

The sum of the shot noise contribution for the two detectors is,

N _(noise) ^(SD) ∝P _(ref) ¹×0.5BW+P_(ref) ²×0.5BW=0.5P _(ref)BW,  (11)

which may compared with the shot noise of a single detector in timedomain OCT,

N_(noise) ^(TD)∝P_(ref)BW.  (12)

Thus, by spectrally dispersing the detection arm light over two separatedetectors, the signal remains the same, while the noise is reduced by afactor of 2, resulting in a net SNR gain by a factor of 2.

Extending the above analysis, it can be demonstrated that the shot noisecontribution is reduced by a factor equal to the number of detectors.The sum of shot noises for N detector elements, where each detectorelement receives one N^(th) of the total reference power, is given by,

$\begin{matrix}{N_{noise} = {\frac{2\eta \; e^{2}P_{ref}}{E_{v}}{\frac{B\; W}{N}.}}} & (13)\end{matrix}$

The signal is the same as in Time Domain OCT, and the SNR ratio forSpectral Domain OCT is given by,

$\begin{matrix}{\frac{S}{N_{noise}} = {\frac{\eta \; P_{sample}N}{2E_{v}B\; W}.}} & (14)\end{matrix}$

Thus Spectral Domain OCT enables a SNR improvement over Time Domain OCTof a hundred to a thousand fold, depending on the number of detectorelements N. Using a charge coupled array or an integrating device as adetector, such as, but not limited to, a line scan camera, the ratioN/BW is replaced by the integration time τ_(i) of the array, whichresults in,

$\begin{matrix}{\frac{S}{N_{noise}} = {\frac{\eta \; P_{sample}\tau_{i}}{2E_{v}}.}} & (15)\end{matrix}$

Advantages

The exemplary embodiment of the present invention reduce shot noise andother forms of noise which allows for much lower source powers, or muchhigher acquisition rates than current systems. The increased detectionsensitivity allows for real time imaging. Such imaging speed can helppractitioners where motion artifacts are a continuing problem, such asin gastrointestinal, ophthalmic and arterial imaging environments. Byincreasing the frame rate while maintaining or improving the signal tonoise ratio such artifacts can be minimized.

The present invention also enable one to screen large areas of tissueswith OCT and allows clinical viable screening protocols using thismethod.

FIG. 2 shows a top level system 100 configuration according to anexemplary embodiment of the present invention, which comprises aninterferometer 102 with a source arm 104, a sample arm 106, a referencearm 108, and a detection arm 110 with a spectral separating unit 112,multiple detectors 114, amplifiers 116, optional analog processingelectronics 118 (not shown, but known to those skilled in the art), andA/D converters 120 (not shown, but known to those skilled in the art)for conversion of signals. A processing and display unit 122 hasoptionally digital band pass filtering (“BPF”) units 124, Digital FastFourier Transforms (“FFTs”) 126 (not shown), coherent combination ofsignals, and data processing and display algorithms. The detector array114 may be 1×N for simple intensity ranging and imaging and/or Dopplersensitive detection, 2×N for dual balanced detection, 2×N for simpleintensity ranging and/or polarization and/or Doppler sensitivedetection, or 4×N for combined dual balanced and polarization and/orDoppler sensitive detection. Alternatively, an M×N array may be used forarbitrary number “M” of detectors 114 to allow detection of transversespatial information on the sample 130.

FIG. 3 shows a schematic of one exemplary embodiment of a SpectralDomain OCT system 200, which includes a light source 202, splitter 204,reference arm 206, sample arm 208, tissue sample 130, optical element210, grating 212, lens 214, detector 216 array, and processor 218. Thedetection arm light is dispersed by the grating 212 and the spectrumimaged onto a detector array 216. By stepping the reference arm 206length over a distance λ/8, the cross spectral density of reference arm206 and sample arm 208 light can be determined. A Fourier transform ofthe cross spectral density generates the depth profile information.

Sources

The source arm 203 contains at least light source 202 that is used toilluminate the interferometer with low-coherence light. The sourcetemporal coherence length is preferably shorter than a few microns (apreferred range is about 0.5 μm-30 μm). Examples of sources include, butare not limited to, semiconductor optical amplifier, superluminescentdiodes, light-emitting diodes, solid-state femtosecond sources,amplified spontaneous emission, continuum sources, thermal sources,combinations thereof and the like. Other appropriate sources known tothose skilled in the art may be used. While light is referred to hereinas the source, it is intended that other electromagnetic radiationranges may be suitable for use, depending on the circumstances.

Interferometer

The sample arm 208 collects light reflected from the tissue sample 130and is combined with the light from the reference arm 206 to forminterference fringes. The reference arm 206 returns light back to becombined with the source arm 203. The reference arm can also betransmissive with no reflection. This action of beamsplitting/recombining may be performed using a beam splitter 204(Michelson), or circulator(s) (Mach-Zehnder) or other means known tothose skilled in the art for separating a beam into multiple paths andrecombining these multiple beams in a manner that interference betweenthe beams may be detected. The splitting may be accomplished in freespace or by using a splitter 204 having passive fiber optic or waveguidecomponents.

Sample Arm

For LCI applications, the sample arm may be terminated by an opticalprobe comprising a cleaved (angled, flat, or polished) optical fiber orfree space beam. A lens (such as, but not limited to, aspherical,gradient index, spherical, diffractive, ball, drum or the like) may beused to focus the beam on or within the sample. Beam directing elements(such as, but not limited to, mirror, prism, diffractive optical elementor the like) may also be contained within the probe to direct thefocused beam to a desired position on the sample. For OCT applications,the position of the beam may be changed on the sample as a function oftime, allowing reconstruction of a two-dimensional image. Altering theposition of the focused beam on the sample may be accomplished by ascanning mirror (such as, but not limited to, a galvanometer,piezoelectric actuator or the like), electrooptic actuator, or movingthe optical fiber (for example, rotating the optical fiber, or linearlytranslating the optical fiber). The sample arm probe may be a fiberoptic probe that has an internally moving element where the motion isinitiated at a proximal end of the probe and the motion is conveyed by amotion transducing arrangement (such as, but not limited to, wire,guidewire, speedometer cable, spring, optical fiber and the like) to thedistal end. The fiber optic probe may be enclosed in a stationary sheathwhich is optically transparent where the light exits the probe at thedistal end. FIG. 4 shows a detail view having an inner cable 260 (whichmay rotate or linearly translate along the axis of the probe), an outertransparent or semi-transparent sheath 262, distal optics 264, andremitted light 266 (which may be at any angle with respect to axis ofcatheter).

Reference Arm Delay

A mechanism 270 in the reference arm 206 allows for scanning the groupdelay of the reference arm 206. This group delay can be produced by anyof a number of techniques known to those skilled in the art, such as,but not limited to, stretching an optical fiber, free spacetranslational scanning using a piezoelectric transducer, or via agrating based pulse shaping optical delay line. Preferably, the delay isintroduced by a non-mechanical or motionless arrangement. By“non-mechanical” it is meant that no mechanically moving parts areutilized. The absence of mechanically moving parts is believed to reducethe known deficiencies of using mechanical devices to introduce delay.As opposed to traditional LCI or OCT systems described in theliterature, the reference arm 206 in the present invention does notnecessarily need to scan over the full ranging depth in the sample, andpreferably scans over at least a fraction of the ranging depth equal toone over the number of detectors (1/N). This scanning feature isfundamentally different from known delay scanning schemes used inconventional known LCI and OCT systems. The reference arm 206 optionallyhas a phase modulator mechanism (described more fully herein), such as,but not limited to, an acoustooptic modulator, electrooptic phasemodulator or the like, for generating a carrier frequency. In order toreduce the scan range of the reference arm 206, the spectrum ispreferably split into a plurality of spectral bands according to amethod that will be explained below.

Detection

Referring to FIG. 2, in the detection arm 110 spectral separating unitseparates the spectral components and the signal is forwarded toseparate detectors 114. The detectors 114 may preferably consist ofphotodiodes (such as, but not limited to, silicon, InGaAs, extendedInGaAs, and the like). Alternatively, a one or two dimensional array ofdetectors 114 (such as, but not limited to, photodiode array, CCD, CMOSarray, active CMOS array, CMOS “smart pixel” arrays, combinationsthereof and the like) may be employed for detection. Two detectors 114for each spectral band may be used for polarization sensitive detectionfollowing separation of the recombined light into orthogonalpolarization eigenstates. Detector 114 arrays may be 1×N for simpleintensity ranging and imaging and/or Doppler sensitive detection, 2×Nfor dual balanced detection, 2×N for intensity ranging and imagingand/or polarization sensitive and/or Doppler sensitive detection, or 4×Nfor combined dual balanced and intensity ranging and/or Dopplersensitive and/or polarization sensitive detection. Alternatively, an M×Narray may be used for arbitrary M to allow detection of transversespatial information on the sample 40.

Detector signals can be amplified by Trans Impedance Amplifiers (“TIAs”)116, band pass filters 124 (digitally or using analog circuitry) anddigitized by A/D converters and stored in a computer 122 for furtherprocessing. Each detector 114 is preferably configured to be shot noiselimited. Shot noise limited detection is preferably achieved byadjusting the intensity of light returned from the reference arm 108 sothat the shot noise dominates over the thermal noise of the resistor inthe TIA 116 and is higher than the relative intensity noise (“RIN”).Each detector 114 is balanced for such dual noise reduction.

In one embodiment of the present invention, the number of detectors 114,N can be in the range of 2-10,000 or more. A preferred range of N isabout 8-10,000 detectors. In one preferred embodiment, eight detectors114 (or a number in that area) can provide real time, or close to realtime, imaging.

Alternatively, another way for detection includes an integratingone-dimensional or two-dimensional detector 114 array which is capableof obtaining images at a rate preferably greater than 1/f noise(f=frequency) (see FIG. 5). Optionally, the BPF can be implementeddiscretely following digitization. An additional modification includesusing an optional second detector 115 array for balanced detection whichallows increased reference arm power and acquisition speed due toreduction of RIN and 1/f noise. In a preferred embodiment, a phasetracking apparatus and/or algorithm is used in the reference arm 108 toreduce signal attenuation due to fringe instability.

This system could be implemented using a single detector 114 withdual-balanced detection enabled by either interleaving dual balancedrows of the array detector or by placing two similar array detectorsadjacent to one another. If two array detectors 114 and 115 are used,the values are subtracted from one another to achieve dual balancedetection. If more than two array detectors are used the signals can beselectively subtracted and complex spectral density can be obtained.

The spectral intensity as a function of wavelength is preferablyconstant. However, if it is not, the spectrum can be shaped in thereference, sample and/or source arms to make it constant. Spectralshapers are known in the art.

Processing

The signal of each detector 114 is band pass filtered around the signalfrequency, such as by FFT's. The signal of all detectors 114 can becombined as explained hereinabove to obtain the complex cross spectraldensity in the frequency domain. By Fourier transform, the complex crossspectral density can be converted to a depth profile in the tissue.Several methods to process the complex spectral density to obtain depthprofile information are known to those skilled in the art, such as, butnot limited to, by obtaining at least two signals with a pi/2 phaseshift in the reference arm and then reconstructing the complex spectraldensity by some linear combination of the two signals.

Following detection analog processing includes a trans impedanceamplifier, band pass filter, and digitization of the signal. This signalmay then be converted to reflectivity as a function of depth by theFourier transform operation. Digital processing includes digitization,digital band pass filtering in either the frequency domain or timedomain (FIR or IIR filter) and inverse Fourier transformation to recoverthe tissue reflectivity as a function of depth.

System Integration

Processing of the multiple signals may be performed using an imaging ordiagnostic console which performs basic operations including,mathematical image reconstruction, display, data storage. Alternatively,another embodiment, shown in FIG. 6, shows a standalone detection andprocessing system 300 that may be connected to OCT and/or LCI systemsalready in use. In this case, the detector 302 and digitization may beperformed in the standalone unit. The input to the standalone unit wouldbe the light combined from both reference and sample arms, as previouslydescribed. The output of the system would be an interferometric signalsimilar to previous OCT or LCI console inputs, but with increased SNR.The standalone unit would contain a splitter 304 for splitting thewavelengths into spectral bands, multiple detectors 302, analogelectronics, including TIA's 306 and an arrangement for reconstructingthe interferometric signal, as previously described. The arrangement forreconstructing the interferometric signal would include either analog ordigital arrangement where the analog arrangement includes band passfilters (“BPF's”) 308, and analog arrangement for adding the individualinterferograms from each wavelength band. The digital arrangement wouldinclude an analog to digital converter, and a CPU 310 capable ofrecombining the interferograms from each spectral band into a singlefull bandwidth interferometric signal. The reconstructed interferogrammay be then the output of the standalone system or alternatively, thereconstructed interferograms demodulated signal may be used as the inputto the pre-existing system console.

Scan Range of the Reference Arm.

The ranging depth in the sample 130 is determined by the resolution withwhich the cross spectral density can be determined. In a method using asingle detector the spectral resolution of the complex spectral densityis determined by the scan range of the reference arm. The larger thescan range, the higher the spectral resolution and the larger theranging depth in the sample. In a system with a spectral separating unitand multiple detectors, the resolution of the cross spectral density isa combination of reference arm scan range and spectral separatingcharacteristics.

Any suitable wavelength band shape may be used for separating. Forarbitrary spectral band shapes, the scan range of the reference arm 18is determined by the delay that is needed to completely resolve thespectral components in each band.

For instance, in one preferred embodiment, as depicted in FIG. 7, aspectral separating unit can split the spectrum into two bands whereeach band consists of a set of narrow spectra in a comb-like structure.FIG. 7A shows the spectral band at detector #1. FIG. 7B shows thespectral band at detector #2. FIG. 7C shows the combined spectral bandof both detectors. Interleaving the comb-like spectral bands of eachdetector 24 gives back a continuous spectrum. The resolution needed toresolve the spectrum at an individual detector is half of what it wouldneed to be in a single detector system, and thus the scan range of thereference arm can be reduced by a factor of two, while maintaining thesame ranging depth in the sample 130. In an alternative embodiment, thespectral separating unit can be in the reference arm. In FIG. 8 anexample is shown for splitting up the spectrum in several spectralbands. In this example the scan range of the reference arm can bereduced by a factor relating to the number of spectral bands whilemaintaining the same ranging depth in the sample.

Embodiments of the Wavelength Separating Filter

Several techniques are known to separate or disperse the spectrum. Onemethod uses a grating and a micro lens array to focus spectralcomponents onto individual detectors. A second method uses prismsinstead of a grating. A third method uses a grating and an addressablemirror array (such as, but not limited to, a “MEMS” mirror or digitallight processing (“DLP”) apparatus or the like) to direct spectralcomponents to individual detectors. A fourth method uses a linear arrayof optical filters prior to the array of individual detectors. A fifthmethod uses waveguides etched into a material or manufactured from fiberoptic components to generate a pattern with the desired filter action.As an example, in FIG. 8 an exemplary embodiment of a wave guide filteris provided that splits the spectrum into bands. A sixth method woulduse arrayed waveguide gratings (“AWG”) to create the interleaved orarbitrary spectral bands.

Relative Intensity Noise

One of the noise terms that is present at the detectors is relativeintensity noise (“RIN”) or Bose-Einstein noise. RIN noise likely becomesdominant over shot noise for spectral widths less than a few nanometers.For many detector configurations, the spectral width at each detectormay likely be smaller than a few nanometers, and the relative intensitynoise can dominate the overall system noise. Thus, balanced detection,can preferably be implemented to eliminate the RIN. Several methodsknown in the art exist to implement balanced detection. One such methodwill be discussed below in further detail. For example, but not by wayof limitation, as shown in FIG. 9, light from the reference arm 400 andsample arm 402 is incident on a grating 404 at slightly different anglesand reflected and focused onto a linear N×M photo detector array 406.Along the N direction (column) of the array, wavelength is encoded.Along the M direction (row) of the array, the interference pattern ofthe sample and reference arm at a particular wavelength is recorded.Since sample and reference arm light were incident at slightly differentangles, a pattern of interference maxima and minima will be present inthe column direction. Balanced detection can be implemented bysubtracting diode signals that are exactly out of phase with respect tothe maxima and minima pattern. Alternatively, balanced detection can beimplemented by measuring the amplitude of the interference pattern inthe column direction which may be accomplished by subtracting the maximaor the interference pattern from the minima of the interference patternalong the column. An alternative embodiment for balanced detection iscombining the reference and sample arm light 400, 402 to produce twooutputs that have interference signals with a π phase shift betweenthem. This may be accomplished by taking both output ports of a beamsplitter or other beam-recombining element. The two signals may then bedetected separately and subtracted. Since the signals that contain theinterference terms are shifted by π in phase, these terms addconstructively upon the operation of subtraction. The portion of signalthat contains RIN, however, cancels upon subtraction. The subtractionoperation can occur for all M elements and be conducted in the analog ordigital domain. If subtraction is performed in the analog domain, thebandwidth of the signal is reduced by a factor of 2, preferablydecreasing specified parameters of the digitization and data transferacross the computer bus.

An example of such balanced detection is shown in FIG. 10, which isdescribed more fully hereinbelow. The balance detection outputs aresubtracted to generate a balanced signal that cancels RIN.

Signal Processing to Reconstruct the Signal after Spectral Separatingand Detection.

Two cases will be discussed below as nonlimiting illustrations ofexemplary embodiments of the present invention, firstly the case ofcontinuous spectral bands (blocks), and secondly the comb-like spectralbands as depicted in FIG. 7

Case A: Continuous Spectral Bands.

The detection arm light is split into N spectral blocks, where eachspectral block contains the intensity between two optical frequencies,

$\begin{matrix}{B_{N} = {\int_{\omega_{N}}^{\omega_{N + 1}}{{S_{ref}\left( {\omega \; {c/2}v} \right)}{\omega}}}} & (20)\end{matrix}$

The signal for the full spectral width is obtained by an FFT of thesignal in each band, an optional compensation of dispersion and othercorrections to the phase and amplitude of each Fourier component tooptimize the signal and to correct the spectral density for side lobereduction, addition of the complex FFT spectra, and inverse FFT on theadded complex FFT spectrum, optionally with data reduction before theinverse FFT, to obtain the optionally demodulated function R(t), whichis the interferometric response for a depth scan with the full sourcespectrum.

Case B1: Comb Like Spectral Bands and the Reconstruction of the FullDepth Range in the Sample Arm from Reduced Reference Arm Scans.

The following description provided below describes the principle ofreconstruction of the full depth range in the sample arm from reducedreference arm scans according to the present invention. The procedureshall be explained in the case of separating the spectrum in twospectral bands. The exemplary method can be expanded for separating intomany spectral bands.

The signal at the detector for a single detector system is defined byR(t). The depth range in the sample is given by the measurement time Tof a single A-line (depth profile) times the group velocity generated bythe reference arm delay line, z_(range)=v_(g)T

The smallest resolvable frequency after an FFT is given by 1/T, whichgives a smallest resolvable angular frequency Δω=2π/T. The filter asdepicted in FIG. 8 splits the signal into two bands with peaks atω=ω₀,ω₀+2Δω,ω₀+4Δω, etc. and ω=ω₀=Δω,ω₀3Δω, etc., respectively.

B₁(t) and B₂(t) are the signals in band one and two respectively. Thesignal in spectral bands one and two after Fourier transform are givenby B₁(ω)=R(ω)cos² (ωT/4) and B₂(ω)=R(ω) sin²(ωT/4).

This product in the Fourier domain can also be written as a convolutionin the time domain. Assuming the signals periodic with time T, thesignals B₁(t) and B₂(t) are given by B₁(t)=R(t)+R(t+T/2) andB₂(t)=R(t)−R(t+T/2).

Using the above equations, the signal R(t) from t=0 to t=T can bereconstructed from the signals B₁(t) and B₂(t) recorded from t=0 tot=T/2 by writing, R(t)=B₁(t)+B₂ (t) and R(t+T/2)=B₁(t)−B₂(t) for0≦t≦T/2. For higher N>2, the identical procedure is performed such thatR(t) is reconstructed from B₁ to B_(N).

This demonstrates that the signals B₁(t) and B₂(t) only need to berecorded over half the depth range z_(range). Thus, the depth ranging inthe reference arm can be reduced by a factor of 2, while the rangingdepth in the sample remains the same. If the signal is split into morespectral bands, like shown in FIG. 7, a similar procedure as describedabove allows reduction of the depth scan in the reference arm by afactor of N, while the ranging depth in the sample remains the same, andN the number of spectral bands.

An exemplary flow diagram of the procedure described above is shown inFIG. 11.

Case B2. Limit of Large Number of Spectral Bands

In the limit of a large number of spectral bands,

${N \geq \frac{L}{\lambda}},$

the optical path length change in the reference arm approaches that of awavelength, λ. In this limit, only a phase change across one wavelengthis needed for reconstructing the entire axial scan over length L. Inthis case, the reference arm path delay may be accomplished by using anyof the aforementioned ways for scanning the reference arm delay. Otherpreferred methods according to the present invention include insertionof an electrooptic modulator, acoustooptic modulator or phase controlrapidly scanning optical delay line (“RSOD”) in the reference arm pathto impart the path length delay of one wavelength. Also in this case,the wavelength separating unit does not separate the wavelengths into acomb pattern, but separates the spectrum into unique opticalfrequencies, with each frequency detected by a single detector.

Case C. Fourier Domain Reconstruction for Arbitrary Wavelength Patterns

In contrast to the reconstruction of the LCI or OCT signal in the timeor space domains, the signal may be reconstructed in the Fourier domainby adding the complex spectral components for each wavelength band tocompose the Fourier transform of the LCI or OCT signal. Alterations ofthe phase for each Fourier component may be preferred in certainselected circumstances to correct for minimization of reference armdelay length.

Reconstruction of the Image or One Dimensional Axial Scan

Following reconstruction of the LCI or OCT signal in the real domain,the axial reflectivity may be determined by demodulating thereconstructed LCI or OCT signal. An arrangement for demodulation caninclude multiplication by a sinusoid and low pass filtering, envelopedemodulation using envelope detection, square law demodulation and lowpass filtering, quadrature demodulation followed by FIR, IIR filtering,or low pass filtering. In addition, the reconstruction of Stokes vectors(polarization) and flow from these LCI or OCT signals is known to thoseskilled in the art. Following reconstruction and demodulation, the datamay be displayed in one or two-dimensional format (image) forinterpretation and ultimately diagnosis of a tissue condition or defectin a medium. If the LCI or OCT signal is reconstructed in the Fourierdomain, such reconstructed signal in the Fourier domain can bedemodulated in the Fourier domain by shifting the Fourier spectrum andperforming an inverse Fourier transform. As a result, the complex signalin the real domain (quadrature signal) is then reconstructed into axialreflectivity information by computing the amplitude of the real portionof the quadrature signal. The complex component is used for computingpolarization or flow information. Alternatively, if the signal isreconstructed in the Fourier domain, it can be directly inverse Fouriertransformed into the real domain and undergo the aforementionedprocessing described for the reconstructed real domain signals.

FIG. 12 shows an exemplary embodiment of a Spectral Domain OCTinterferometer design 500 showing spectral compounding of light sources502, 504, and 506 and acousto-optic generation of the carrier in thereference arm. The blocks labeled AOM are acousto-optic modulators 508,510. The two outputs each go to separate spectral detection units 114,115 (as depicted in FIGS. 3 and 13) for balanced detection.

After spectral compounding of the source light in the first 50/50splitter and the 80/20 splitter, light enters a modified Michelsoninterferometer. A configuration that implements balanced detection isshown. The sample arm goes to the probe (e.g., a slit lamp). Referencearm light is transmitted through two acousto-optic modulators with adifference frequency of 10 kHz to generate a constant carrier frequencythat is independent of wavelength. The balanced detection outputs go toseparate spectral detection units.

Spectral Detection Unit

Referring to FIG. 13, the core of Spectral Domain OCT is spectralseparation of the detection arm light onto a multi-element array 114.The detection arm beam 520 is spectrally separated by a grating 520 andfocused by a lens 522 onto a multi-element array 114.

A scan cameras with N detector elements is used as spectral detectionunit 128 (see FIG. 2). Preferably, balanced detection is implemented byadding a second line scan camera. As is known to those skilled in theart, the depth range is inversely proportional to the spectralresolution. When the real part of the complex spectral density isdetermined, ranging depth z is defined by,

$\begin{matrix}{{z = \frac{\lambda_{0}^{2}}{4{\Delta\lambda}}},} & (18)\end{matrix}$

Line scan rates of 20 kHz can be achieved, allowing demodulation of a 10kHz carrier to extract the complex cross-spectral density. Data isdigitized and transferred to computer memory. Demodulation of the signalis done in software. Scan rates of 10,000 depth profiles per second ormore can be achieved.

Dual Balanced Detection

Dual balanced detection is preferably used by the present invention,which is preferably utilized for the following reasons. Firstly, mostlight sources generate 1/f noise (f=frequency) at relatively lowfrequencies. Balanced detection will eliminate 1/f source noise.Secondly, an interference term of the sample arm light with itself(auto-correlation term) is present on top of the true signal term, whichis the interference between sample and reference arm. Thisauto-correlation term can be eliminated by a differential technique.Balanced detection may eliminate this auto-correlation term from themeasured signal. Thirdly, RIN can be reduced.

Data Acquisition and Processing Unit

The data rate at 20,000 spectral profiles per second, with 2000 detectorelements and 8-10 bit resolution (the dynamic range of most line scancameras) is 40-80 MB/sec. Maximum sustainable data transfer speed overthe PCI bus is 100 MB/sec. In a computer with two independent PCIbridges to computer system memory, approximately 200 MB/sec of data canbe transferred for real time processing of data from two line scancameras simultaneously. Implementation of dual balanced detection inanalog by subtracting line scan camera signals before digitization mayreduce the data rate by a factor of 2. High-speed data acquisitionboards are available at resolutions of 12-14 bits and speeds up to 100Msamples/sec. A single 2048 point fast Fourier transform on a 2.5 GHzPentium 4 processor takes 50 μsec. These numbers show that real-timeprocessing of Spectral Domain OCT data at 20,000 spectral profiles/secis within reach of current data acquisition and processing power of dualprocessor PC's. The data collected by the spectrometer can be sampledwith equal wavelength increments. Fourier transform, however, links zand k space (or t and w). Because of the non-linear relation between kand λ the spectrum from the spectrometer should be interpolated tocreate evenly spaced samples in k domain. To achieve the optimal pointspread function, dispersion in the sample and reference arm of theinterferometer should be balanced. We have shown that dispersionimbalance can be corrected for by digital processing, allowing forcorrect compensation of dispersion for individual eye lengths.

Phase Tracking

The present invention also provides apparatus and methods for phasetracking in spectral domain (“SD”) OCT.

Fully Parallel SD OCT

One of the features of fully parallel SD OCT is spectral dispersion ofthe detection arm light onto a multi-element array such as but notlimiting to an integrating device (e.g., CCD) and measurement of thereal or complex spectral density at high speeds. The detection arm beamis separated by a spectral separating unit (e.g., grating) and focusedonto the array. With respect to previous Spectral Domain OCT designsknown in the art, two differences are apparent that will be discussedbelow: 1) implementation of balanced detection, and, 2) implementationof phase tracking.

Spectrometer design The depth range in SD OCT is inversely proportionalto the spectral resolution. Using the complex spectral density, rangingdepth z is given by,

$\begin{matrix}{z = {\frac{\lambda_{0}^{2}}{2n\; {\Delta\lambda}}.}} & (18)\end{matrix}$

Dual balanced detection: Dual balanced detection is advantageous for atleast three reasons. First, most light sources generate 1/f noise atrelatively low frequencies (tens of kHz range). In time domain (“TD”)OCT systems 1/f noise is not a problem because the signal carrier is ingeneral in the MHz range where 1/f noise is not significant. In SD OCT,balanced detection may likely eliminate 1/f source noise. Second, aninterference of the sample arm light with itself (auto-correlation term)is present on top of the true signal. This auto-correlation term can beeliminated by a differential technique. Balanced detection can be usedto eliminate this auto-correlation term from the measured signal. Third,balanced detection may reduce relative intensity or Bose Einstein noise.

Phase Tracking: Phase tracking is preferable to eliminate phaseinstabilities in the interferometer. Phase instabilities can causeindividual interferometric fringes to shift in location. If detection isslow relative to the shifting of the fringes, the resulting averagingresults in an artifactual decrease in the measured fringe amplitude.Fast detection arrays can capture the cross spectral density at a rateof 20 to 40 kHz, resulting in integration times of 50 to 25 μsec,respectively. Phase instabilities arising on a time frame shorter thanthe integration time of the array should be compensated.

FIG. 14 shows an exemplary interference pattern as a function of pathlength difference between sample and reference arm.

Phase locking circuitry is common in electronics, and is frequently usedin radar and ultrasound. Active phase tracking can be implemented bymodulating the interferometer path length difference at 10 MHz with anelectro-optic phase modulator in the reference arm over a fraction ofthe wavelength. By demodulating the intensity measured by one detectorat the output of the interferometer at the frequency of the path lengthmodulation, an error signal can be generated indicating in whichdirection the phase modulator should shift to lock onto a fringeamplitude maximum. By adding an offset to the phase modulator asdetermined by the error signal, the phase tracker actively locks onto afringe maximum. The phase modulator can only modulate the path lengthdifference over a few wavelengths. The processing unit can determine ifthe phase modulator has reached its range limit, and jump by a full wavein phase to maintain lock on a different fringe maximum. This approachexploits the fact that phase should be controlled only modulo 2π. Inaddition, the processing drives a slower component (e.g., the RapidScanning Optical Delay line) to extend the path length range of thephase modulator/RSOD combination over several millimeters. Phase lockingcan be performed on a fringe maximum, minimum, or zero crossing, basedon the type of mixing performed in the demodulation circuit.

The present invention can also use autoranging technology, includingprocessing algorithms, as disclosed in copending U.S. application Ser.No. 10/136,813, filed Apr. 30, 2002, entitled METHOD AND APPARATUS FORIMPROVING IMAGE CLARITY AND SENSITIVITY IN OPTICAL COHERENCE TOMOGRAPHYUSING DYNAMIC FEEDBACK TO CONTROL FOCAL PROPERTIES AND COHERENCE GATING,and commonly assigned to the assignee of the present invention, thedisclosure of which is incorporated herein.

The autoranging mechanism may, in one exemplary embodiment, comprise aprocessor unit for (a) obtaining a first scan line; (b) locating asurface location “S” of a sample; (c) locating an optimal scan range “R”of the sample; (d) modifying a reference arm delay waveform to providean output; (e) outputting the output to a reference arm; (f) determiningwhether the image is complete; and (g) moving to the next scan line ifthe image is not complete or remapping the image using the surface Sdata and the waveform data stored in the memory storage device if theimage is complete.

If the light returned from the sample is of low amplitude, phase lockingmay be unstable due to the presence of noise. In another embodiment, aseparate, preferably monochromatic, light source is input into theinterferometer. The separate source wavelength may overlap with thebroad bandwidth OCT or LCI source spectrum or may be centered at adifferent wavelength than the OCT or LCI source spectrum. The separatesource is preferably of higher power and may be combined with the sourcearm (using wavelength division multiplexer, grating, prism, filter orthe like) travel to the reference and sample arms and return back to thebeam recombining element. The returned separate source light can thenseparated from the OCT or LCI light following transmission back throughthe beam recombining element (i.e. beam splitter output). A separationarrangement can perform spectral separation by a dispersing element,such as a dichroic mirror, filter, grating, prism, wavelength divisionmultiplexer or the like. The separate source will be detected separatelyfrom the OCT or LCI broad bandwidth light using one or more detectors.The higher power provided by this separate source can enable detectionof a higher amplitude interference pattern, and provide an improvedinput to the phase tracker, thus enabling more stable phase tracking.

FIG. 15 shows one exemplary embodiment of a phase tracker system 600according to the present invention with an extended phase lock range, bycombining a fast element (EO phase modulator) 602 to modulate the pathlength difference over a small range, and a slower element (RSOD) 604 tomodulate the path length over an extended range. The detector 606 signalis mixed with the phase modulator modulation frequency 608 by a mixer610 and low pass filtered (filter not shown) to generate an errorsignal. The processing unit 612 preferably processes the error signal togenerate an offset voltage, and adds this offset voltage to themodulation signal 608, so as to generate the output for the phasemodulator driver 614. In addition, the processing unit 612 can generatea signal to the RSOD 604 to provide extended range tracking of the phaseover distances of several millimeters. Light source 616, fiber splitter618, sample arm 620 and reference arm 622 are shown, and are describedherein.

Mixer Implementation: The intensity I(t) at the detector at a givenmoment within a single oscillation of the fringe pattern is given by

I(t)=cos [φ(t)]

where the phase φ gives the position in the fringe. For φ=0, the signalis at a fringe maximum, for φ=π, the signal is at a fringe minimum. Atan arbitrary moment t, the phase φ(t) is given by,

φ(t)=α+β sin(ωt)

where α describes the position within a single oscillation of the fringepattern, and β*sin(ωt) is the phase modulation introduced by the phasemodulator, with β the amplitude of the phase modulation, and ω thefrequency of the phase modulation signal. The intensity at thephotodetector I(t) can be mixed with a carrier at frequency ω and 2ω,resulting in the mixer signal MixerC(t), MixerS(t), Mixer2ωC(t) andMixer2ωS(t),

MixerC(t)=cos(ωt)*cos(α+β sin(ωt)); MixerS(t)=sin(ωt)*cos(α+β sin(ωt))Mixer2ωC(t)=cos(2ωt)*cos(α+β sin(ωt)); Mixer2ωS(t)=sin(2ωt)*cos(α+βsin(ωt))

The time average over a single oscillation of the carrier frequency ω ofMixerC, MixerS, Mixer2ωC and Mixer2ωS is given by,

MixerC(t)=0; MixerS(t)=sin(α)*J ₁(β); Mixer2ωC(t)=cos(α)*J ₂(β);Mixer2ωS(t)=0

where J₁(β) and J₂(β) are a Bessel functions of the first kind; itsvalue depends on β, the amplitude of the phase modulation. Thus, thesignal MixerS(t) and Mixer2ωC(t) are proportional to sin(α) and cos(α),respectively, with a the position within a single oscillation of thefringe pattern. The mixer outputs MixerS(t) and Mixer2ωC(t) are used asan error signal to generate an offset voltage to steer the phasemodulator to a new center position that minimizes the error signal, andlocks the interferometer output on a fringe maximum or minimum, or azero crossing, respectively. The complex spectral density can now bedetermined by two consecutive array scans, one where the error signalsin(α) is minimized, and the next where the error signal cos(α) isminimized, resulting in a 90 degrees phase shift between the twointerference patterns. Using this mixing arrangement, the complexspectral density can be obtained rapidly and without resorting to anadditional mechanical arrangement for changing the phase of thereference arm light.

FIG. 10 shows one exemplary embodiment of a SD OCT system 700 with phasetracker for providing balanced detection according to the presentinvention. In this embodiment, a source 702 provides light which passesthrough a splitter 704, which sends part of the light to a sample probe706 and the remainder of the light to a Rapid Scanning Optical Delay(“RSOD”) line 708. Light is passed from the RSOD 708 to the phasemodulator PM 710. Light from the phase modulator PM 710 is sent througha splitter 712, and then through two additional splitters 714 and 716, aportion of the output of which is sent as balanced detection outputs tospectral detection units (not shown, but as described elsewhere herein)and the remainder of the output is sent to the phase tracker assembly720. In the phase tracker assembly 720, phase tracker detectors D₁ andD₂, 722 and 724, receive the partial output of the pair of splitters 714and 716, which in turn send signal to a mixer 726 to generate an errorsignal. A processing unit 728 processes the error signal, where the sumgeneration of offset voltage and adds this to the modulation signal 730to generate the output for the phase modulator driver 732. Modulationsignal, shown at box 730, is forwarded to the mixer 726 and theprocessing unit 726. In addition, the fringe amplitude could be toosmall for the phase tracker to lock. Alternatively, a secondary sourcewith longer coherence length could be coupled to the system 700 toprovide a larger fringe amplitude to the phase tracker.

The present invention provides a method for tracking phase in an imagingsystem, as shown in FIGS. 15A-C the method comprising the steps of: (a)measuring a signal received from the sample arm; (b) increasing a phaseof the signal; (c) measuring a first signal partition of the signaldefined as x₁ at least one peak of the signal; (d) determining whetherto increase or decrease the phase of the signal by an incrementalamount; (e) after step (d), measuring a second signal partition of thesignal following step d); and, if the signal is at its peak, remeasuringthe signal and if the signal is not at its peak, repeating steps d) ande).

The method further may comprise that steps (a)-(f) are performed inparallel with other imaging processes. The adjustment of phase “φ” isdefined as A(x₂-x₁), where “A” is a constant. Furthermore, optionally,step d) may further comprise the substeps of d1) determining whetherA(x₂-x₁) is within range of the phase modulator; and d2) changing φ byan amount equal to A(x₂-x₁) if A(x₂-x₁) is within the range or changing(p by an amount equal to A(x₂-x₁)−m2π if A(x₂-x₁) is outside of therange, where M is an integer greater than 1. The method may optionallyfurther comprise a substep d3) remeasuring signal x₁.

Data Acquisition and Processing Unit

In general, the data collected by the spectrometer are sampled withequal wavelength increments. Fourier transform, however, links z and kspace (or t and w). Because of the non-linear relation between k and λthe acquired spectrum is interpolated to create evenly spaced samples inthe k domain. Alternatively, the light could be dispersed in such a wayon the detection array that the light is samples in equal intervals in kspace, such that the interpolation becomes obsolete. Alternatively, thedetection array spacing could be designed to sample the light evenlyspread in the k domain, such that the interpolation becomes obsolete. Toachieve the optimal point spread function, dispersion in the sample andreference arm of the interferometer should preferably be balanced.Dispersion imbalance can be corrected by digital processing.

The present invention provides a probe for locating atheroscleroticplaque in a blood vessel, comprising: an interferometer; a spectralseparating unit which splits signal received from the interferometerinto a plurality of optical frequencies; and a detector arrangementcapable of detecting at least a portion of the optical frequenciesreceived from the spectral separating unit.

The present invention further provides an apparatus for delivering atherapeutic agent, comprising: a probe disposed in the housing andcomprising: an interferometer, a spectral separating unit which splitssignal received from the interferometer into a plurality of opticalfrequencies, a detector arrangement capable of detecting at least aportion of the optical frequencies received from the spectral separatingunit; and a conduit cooperating with the probe, and comprising aproximal end for receiving the therapeutic agent and a distal end fordelivering the therapeutic agent at a predetermined location, thelocation being determined by imaging the environment in proximity to thedistal end using the probe.

An exemplary embodiment of the present invention will be furtherdescribed below in connection with the following example, which is setforth for purposes of illustration only.

EXAMPLE

The method according to the present invention was verified in thelaboratory by the following experiment.

In the existing OCT system, the shot noise power spectrum as determinedfrom the spectral density due to the reference arm optical power wasmeasured. Then ⅔ of the spectrum from the reference arm was blocked, andexperimentally it was verified that the shot noise power spectrum wasreduced by a factor of three, thus demonstrating that the shot noise isreduced by a factor of 3 if the spectrum is split in three spectralbands (see FIG. 16). The upper curve (gray dotted line) shows the powerspectrum for the OCT signal with one detector. For the lower curve(solid line), the spectrum was limited by ⅓ with a corresponding factorof 3 improvement in signal to noise ratio. This data was generated byexperiment, blocking ⅔ of the spectrum in a grating-based double-passedpulse shaping rapidly scanning optical delay line.

An object with low reflectivity was inserted in the sample arm. Usingthe full spectral width of the source, the power spectrum of theinterference between sample and reference arm light was determined inthe lower half of the spectral density. Then the upper part of thesource spectrum was blocked in the reference arm, and it was verifiedthat the lower ⅓ of the power spectrum of the interference betweensample and reference arm light had the same magnitude as in the previousmeasurement (see FIG. 17). This figure demonstrates that the signalamplitude is equal for the N=1 and N=⅓ cases where they overlap. Theresult of equal amplitude signal for N=⅓ case and the 3-fold lower noisefor the N=⅓ case (see FIG. 6) demonstrates that splitting into Nwavelength bands increases the SNR by a factor of N.

This demonstrates that when the light in the detection arm is split intwo spectral bands, the spectral density of the interference betweensample and reference arm light within the spectral bandwidth of a singledetector is unchanged. Combined with the measurement that showed areduction in the shot noise power spectrum, the conclusion is that areduction of shot noise can be realized by splitting the detection armlight in separate spectral bands.

Experimental Verification of the Noise Reduction.

To demonstrate the noise reduction in Spectral Domain OCT, an OCT systemwas used, including a Rapid Scanning Optical Delay line (RSOD) was usedin the reference arm, enabling portions of the spectrum to be blocked.Detector signals were digitized at 2.5 Msamples/sec, allowing digitalprocessing of the fringe information. First, the thermal noise densityof the detector was measured as a function of frequency by blocking alllight onto the detector. Second, the shot noise density of the referencearm power was measured with only the reference arm power incident on thedetector. Third, both the sample and reference arm light were incidenton the detector. The sample was a single scattering surface mounted in amodel eye and 512 depth profiles were acquired in 2 seconds. The powerdensity I(f)² was measured, which is proportional to the spectraldensity squared (see Eq. (9)). Then we blocked half of the spectrum inthe reference and measured again the shot noise density of the referencearm by blocking the sample arm, and the power density I(f)² when bothsample and reference arm light were incident on the detector. Shot noiseand power densities were corrected for thermal noise by subtraction.Thermal noise was at least a factor of 3 smaller than the lowest shotnoise level.

FIG. 18 shows a graph of power density for the full spectrum, and withhalf of the spectrum blocked in the reference arm, as a function offrequency. The solid line shows the power density for the full spectrum.The shot noise level measured while the sample arm was blocked is alsoshown. The dashed line shows the power density with half the spectrumblocked in the sample arm. The shot noise level measured while thesample arm was blocked is also shown. FIG. 18 demonstrates that the shotnoise level was reduced by a factor of 2 by blocking half the spectrumin the reference arm. At the same time, the signal at frequenciescorresponding to wavelengths that were not blocked in the reference armremained the same.

As is evident from FIG. 18, which summarizes the measured results, theshot noise density is reduced by approximately a factor of 2 by blockinghalf the spectrum in the reference arm. FIG. 19 shows that aftersubtraction of the shot noise levels from the corresponding signals, thepower densities for those frequencies that corresponded to wavelengthsthat were not blocked in the reference arm remained the same. Thisdemonstrates that the shot noise density is reduced by a factor of 2when the total reference arm power is reduced by a factor of 2 byblocking half the spectrum, while the signal power density for wavelengths not blocked in the reference arm remains unchanged.

FIG. 19 shows a graph of the square root of the power densities for thefull spectrum, and for half the spectrum blocked in the reference arm asa function of frequency. The solid line shows the spectrum aftersubtraction of the respective shot noise. The dashed line shows the halfspectrum after subtraction of the respective shot noise. FIG. 13demonstrates that after subtracting the respective shot noisecontributions, the signal at frequencies corresponding to wave lengthsthat were not blocked in the reference arm remained the same.

The next experiment further demonstrated that by dispersing the spectrumin the detection arm over several detectors, and by selectively bandpass filtering the signals of each detector, the SNR is increased. Thedetection arm light was dispersed over 4 detectors by a diffractiongrating as shown in FIG. 13, and the detector signals were separatelyamplified by transimpedance amplifiers with a bandwidth of 600 kHz andsimultaneously digitized.

FIG. 13 shows a schematic of an exemplary apparatus setup used todemonstrate SNR improvement by Spectral Domain OCT according to thepresent invention. Scanning of the reference arm 106 was performed witha Rapid Scanning Optical Delay line (RSOD) 120. Individual signals fromthe array detector 114 were amplified by transimpedence amplifiers,digitized by a 4-channel 2.5 MHz per channel A/D board and stored incomputer memory (not shown).

First, the thermal noise density of all four detectors was measured.Second, the shot noise density of the reference arm light in eachdetector channel 116 was measured. Third, both the sample and referencearm light were incident on the detector 114. The sample 130 was a singlescattering surface mounted in a model eye and 512 depth profiles wereacquired in 2 seconds. The power density I(f)² in each detector channel114 was measured. Then, the signals of the four detectors 114 weresummed, and the combined power density I(f)² was determined. The resultsare shown in FIG. 20, which demonstrates that the shot noise is lower ineach individual channel compared with the sum of all channels, but thatthe power densities I(f)² in the individual channels within theirrespective bandwidths are approximately equal to the power density I(f)²of the coherent sum of the four channels.

FIG. 20 shows a graph of the power densities for four separate detectors116 of FIG. 13. The spectrum in the detection arm was dispersed overfour separate detectors 116 by a diffraction grating 520. The shot noiselevels for each individual detector 116 are significantly lower than forthe coherent sum of the four detector channels. Bars at the top of theimage indicate the signal pass band that was applied to the individualchannels and the coherently summed channel to generate FIG. 21.

In FIG. 21, the square of the coherence envelope is shown for both thedirect sum of all four detection channels and the coherent sum afterdigitally band pass filtering each detector channel with a bandwidthcentered at the center frequency of the respective detector signal. FIG.21 shows that the interference fringe signal I(t) of the direct sum andthe band pass filtered coherent sum of the four detector signals resultsin virtually the same coherence envelope peak value, while the band passfiltered coherent sum of the four detector signals shows a significantlylower noise level than the direct coherent sum. Since the pass band ofeach individual channel was slightly larger than one third of the passband of the full signal (pass bands are indicated in FIG. 20), anincrease of SNR of a factor of 2.87 was expected. The noise leveldropped by a factor of 2.8. However, band pass filtering also reducedthe signals slightly, by a factor of 1.12, resulting in an effectiveincrease in SNR of a factor of 2.5.

These experiments clearly demonstrate that spectrally dispersing thelight in the detection arm can offer a significant SNR advantage.

FIG. 21 shows a plot of the coherence envelope for the coherently summedchannels, and the coherently summed channels after band pass filteringeach channel. The solid line is the sum of channels. The dashed line isthe pass filtered sum of channels. FIG. 21 clearly demonstrates thesignal to noise gain that can be achieved by spectrally dispersing thesignal in the detection arm over several individual detectors. In thisexample the noise level was reduced by a factor of approximately 2.8.Since the coherence peak was reduced by a factor of 1.12 due to someremaining signal fraction filtered out by the band pass filters, theactual SNR improvement was 2.5.

Although only a few exemplary embodiments of this invention have beendescribed in detail above, those skilled in the art will readilyappreciate that many modifications are possible in the exemplaryembodiments without materially departing from the novel teachings andadvantages of this invention. Accordingly, all such modifications areintended to be included within the scope of this invention as defined inthe following claims. It should further be noted that any patents,applications and publications referred to herein are incorporated byreference in their entirety.

1-102. (canceled)
 102. An apparatus for optical imaging, comprising: a)an interferometer; b) a spectral separating unit which splits signalreceived from the interferometer into a plurality of opticalfrequencies; c) a plurality of detectors, each detector having acapability of detecting at least a portion of the optical frequenciesreceived from the spectral separating unit; and d) an arrangement whichconfigured to at least one of: i. reconstruct the signal from thedetectors by a mathematical manipulation of each plurality of signalsobtained from the detectors, or ii. track a phase of the signal of theinterferometer.
 104. The apparatus according to claim 103, wherein thearrangement reconstructs the signal from the detectors by themathematical manipulation.
 105. The apparatus according to claim 103,wherein the arrangement track the phase of the signal of theinterferometer.
 106. The apparatus according to claim 103, wherein thespectral separating unit comprises the at least one of (i) theaddressable mirror array, (ii) the linear array of optical filters,(iii) the waveguide filter, or (iv) the waveguide gratings.
 107. Theapparatus according to claim 103, wherein the spectral separating unitsplits the signal into the bands.
 108. The apparatus according to claim103, wherein the detectors are provided in a form of a two-dimensionalarray.
 109. The apparatus according to claim 103, wherein the sample isscanned in a series of simultaneous illuminations of substantially allof the area of the sample.
 110. The apparatus according to claim 103,further comprising the polarization separating unit.
 111. The apparatusaccording to claim 103, wherein the spectral separating unit at leastone of: i. comprises at least one of (i) an addressable mirror array,(ii) a linear array of optical filters, (iii) a waveguide filter, or(iv) waveguide gratings, or ii. splits the signal into a plurality ofbands, whereby at least one of the bands comprises spectra that has acomb-like structure.
 112. The apparatus according to claim 103, whereinthe sample is scanned in a series of simultaneous illuminations ofsubstantially all of the area of the sample.
 113. The apparatusaccording to claim 103, further comprising an arrangement generating apath length difference that is a fraction of a ranging depth of theinterferometer.
 114. An apparatus for tracking a phase of at least oneelectromagnetic signal so as to reduce an attenuation of the at leastone signal due to its fringe instability, comprising: a processingarrangement configured to: a. receive information associated with the atleast one signal, b. adjust the phase of the at least one signal, c.obtain a position of a signal section of the at least one signal, d.modify at least one characteristic of the at least one signal if theposition of the signal section is provided away from a peak of the atleast one signal by more than a predetermined distance, and e. repeatsteps (c) and (d) until the at least one signal is within thepredetermined distance from the peak.
 115. The apparatus according toclaim 114, wherein the information corresponds to a combination of atleast one of the spectral bands which are separated from the at leastone electromagnetic signal by a spectral separating arrangement.
 116. Alogic arrangement for tracking a phase of at least one electromagneticsignal so as to reduce an attenuation of the at least one signal due toits fringe instability, which, when executed by a processingarrangement, configures the processing arrangement to execute the stepscomprising of: a) receiving information associated with the at least onesignal; b) adjusting the phase of the at least one signal; c) obtaininga position of a signal section of the at least one signal; d) modifyingat least one characteristic of the at least one signal if the positionof the signal section is away from a peek of the at least one signal bymore than a predetermined distance; and e) repeating steps (c) and (d)until the at least one signal is within the predetermined distance fromthe peak.
 117. A method for tracking a phase of at least oneelectromagnetic signal so as to reduce an attenuation of the at leastone signal due to its fringe instability, comprising the steps of: a)receiving information associated with the at least one signal; b)adjusting the phase of the at least one signal; c) obtaining a positionof a signal section of the at least one signal; d) modifying at leastone characteristic of the at least one signal if the position of thesignal section is away from a peek of the at least one signal by morethan a predetermined distance; and e) repeating steps (c) and (d) untilthe at least one signal reaches a further position that is within thepredetermined distance from the peak.
 118. A storage medium includingexecutable instructions thereon for tracking a phase of at least oneelectromagnetic signal so as to reduce an attenuation of the at leastone signal due to its fringe instability, wherein, when the executableinstructions are executed by a processing system, the executableinstructions configure the processing system to perform the stepscomprising of: a) receiving information associated with the at least onesignal; b) adjusting the phase of the at least one signal; c) obtaininga position of a signal section of the at least one signal; d) modifyingat least one characteristic of the at least one signal if the positionof the signal section is away from a peek of the at least one signal bya predetermined distance; and e) repeating steps (c) and (d) until theat least one signal is within the predetermined distance from the peak.